Control of the estrous cycle in mammalian species of commercial interest, such as cattle, has a great impact on the efficiency of meat and milk production. Numerous treatments and protocols have been successful in achieving the goal of timely control of the occurrence of several reproductive events such as luteolysis, estrus and ovulation (Kim, Suh et al., 2005; Martinez, Kastelic et al., 2007; Harper, Bennett et al., 2008). However, the application of many of these protocols involves the administration of hormonal combinations in food producing animals, many of which are perceived as having a negative impact on consumer health (Daxenberger, Ibarreta et al., 2001; Galbraith, 2002; Kolok & SeIlin, 2008). The situation has led to the legal banning of steroid hormones within particular geographic locations (i.e., European Union, New Zealand, and Australia) or physiological categories of animals (i.e., lactating dairy cattle; (Official Journal of the European Union; Lane, Austin et al., 2008)).
Aromatase inhibitors are compounds that prevent the body from producing estradiol by inhibiting the activity of the aromatase enzyme that is responsible for the conversion of androgens into estrogens (Buzdar, Robertson et al., 2002; Buzdar, 2003). Aromatase inhibitors are used widely for the treatment of estrogen-responsive breast cancer in postmenopausal women (Beatson, 1983; Geisler, Haynes et al., 2002).
Recent studies have revealed the potential of aromatase inhibitors as a tool to control the estrous cycle in cattle (Yapura et al., 2011a; Yapura et al., 2011; Yapura et al., 2011b; Yapura et al., 2011c). These studies have focused on the use of letrozole, which has been the compound of choice for treatment of sub-fertility or infertility in women (Requena, Herrero et al., 2008). Letrozole treatment in cattle extended the lifespan of the dominant follicle, delayed the emergence of the next ovarian follicular wave, and altered the timing of ovulation. Letrozole treatment also had a consistent luteotrophic effect; i.e., development of a larger corpus luteum that produced more progesterone
The intravaginal route of administration of letrozole is of particular interest because it allows for extended treatment protocols, it is minimally invasive for the animal, it reduces animal handling and treatment-associated stress, and is most likely to be accepted by practitioners and producers.
It is desirable to develop compounds, compositions, methods and devices, which provide an extended release of an aromatase inhibitor(s).
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should it be construed, that any of the preceding information constitutes prior art against the present invention.